Cytomegalovirus (CMV): Primary or Recurrent Infection?
Wednesday, September 27, 2006
Kenneth F. Trofatter, Jr., MD, PhD
CMV grows very slowly and the incubation period from the time of exposure to onset of symptoms, or asymptomatic excretion of the virus, is on the order of 4-12 weeks. Serologic testing, which we will discuss in a minute, can often help to confirm a primary infection when it is obtained coincident with maternal symptoms. Virus detection by culture, immunofluorescent techniques, or polymerase chain reaction (PCR), best done by sampling maternal urine, may be positive (and almost always will be for months after a primary infection), but this alone does not tell us if this is a primary symptomatic CMV infection or a recurrent infection accompanying another illness.
Unfortunately, since such a high percentage of primary maternal infections are asymptomatic, or simply confused with another illness, or even written off as normal symptoms of pregnancy, usually the diagnosis is not suspected until the baby is found to be growth restricted or has subtle physical abnormalities, or a thickened placenta, to suggest it has either a chromosomal abnormality or a congenital infection, sometimes months after the maternal exposure. Under these circumstances, maternal serologic testing might not be helpful in establishing either the fetal diagnosis or the diagnosis of a primary maternal infection during pregnancy.
Establishing the presence of fetal infection requires an 'invasive' procedure. Performing a simple amniocentesis, and using any of the techniques noted above for virus detection, can confirm fetal infection with CMV in nearly 100% of cases. (Remember, the amniotic fluid from midtrimester on is mostly fetal urine, and CMV is excreted in large amounts from the kidneys following congenital infection, and often for years afterwards, even in 'asymptomatic' cases). However, unless we have confirmatory maternal serologic information, or symptomatic infection confirmed to be the result of CMV during the pregnancy, we still may not know if the congenital infection is the result of primary or recurrent maternal disease. If the diagnosis of CMV is not suspected until late in pregnancy, or not until after the birth of the baby, detection of CMV in a urine sample taken from the baby within the first two weeks' of life also suffices to confirm congenital infection. CMV is a VERY slow growing virus, so any detection of virus in this time frame most certainly represents intrauterine infection.
Now let's discuss serologic testing because this is where things become even more confusing with CMV. Usually, when we contract a virus infection like the flu, our immune systems react by first producing specific antibodies to the virus of the IgM class. These usually hang around only for no more than 2-4 weeks after the infection has been cleared. Shortly after IgM antibodies begin to be made, our bodies switch to the production of a second class of specific antibodies called IgG. IgG antibodies generally hang around for a long time after the infection is cleared and provide us with a source of 'permanent immunity' to the organism, helping to prevent reinfection, or decrease the severity of a secondary infection, with the same or similar organisms with which the antibodies might 'cross-react.'It is these IgG antibodies that also afford protective immunity to the baby because they can cross the placenta whereas IgM antibodies cannot.
We can use this information to help us to characterize the status of an infection. If neither IgM nor IgG is present, the individual has probably never been exposed to the organism of concern (or is too early in the course of the infection to have mounted any antibody response). If IgM is present and there is no IgG, then the infection is probably a 'primary' infection, indicating first time exposure to the organism, usually very early in its course. If both IgM and IgG are present, this also usually reflects a primary infection, but later in the course of the disease. And, if only IgG is present, then this indicates a state of permanent immunity established from an infection that occurred at some time in the past. In any of the first three circumstances, if an infection with a specific organism is suspected and could be of concern for a pregnancy, it is probably worth repeating the antibody titers in 4-6 weeks. In the case of CMV, IgG antibodies usually can be detected by 1-2 weeks after the onset of symptomatic infections, but because of the long incubation period of CMV, this might be a month or more after actual exposure to the virus. Rising and falling antibody titers can also help to characterize the status of an infection.
With CMV infections, things are a little trickier. The presence of IgM in the absence of IgG and in the presence of symptomatic disease (or a history of recent exposure to a known carrier) is highly presumptive of a true 'primary infection.' Similarly, the findings of both IgM and IgG with a significant rise (four-fold or more) in IgG titers (with or without a fall in IgM titers) on a follow-up screen 4-6 weeks later, usually (but not always in the case of CMV) indicates a recent primary infection. Also useful, the presence of IgG in the absence of IgM, is highly suggestive of a remote exposure to the virus, often greater than 6 months previously.
The rub with serology in classifying CMV infections comes in most often when IgM is present but IgG titers are relatively stable or mildly fluctuating. Unlike most common viral infections, CMV-specific IgM can sometimes persist 6-9 months following its appearance. And to make things even more confusing, IgM has been found to reappear on occasion with reactivation of latent CMV infections. In otherwords, except in the circumstances detailed above, we may not be able to use the presence of IgM in our counseling to tell patients that they have had a primary or recurrent infection during the pregnancy or if the infection might have occurred even prior to the current pregnancy.
Ascertaining the status of a maternal infection as primary or recurrent, when we can do it, helps in counseling the patient. Babies contracting CMV as the result of recurrent infections are much less likely to suffer the severe sequelae associated with congenital CMV. Congenital CMV infections associated with primary maternal infections early in pregnancy and accompanied by growth restriction and detectable abnormalities by fetal ultrasound, generally, have a very poor prognosis, but even then, the outcome is not entirely predictable....
31 Comments:
At Tue Jul 10, 12:43:00 PM 2007,
angel said…
my son was born with congenital cmv and was given 2 months to live however a year on he is doin well and is only partially deaf and sighted,nothing we cant get through together
At Fri Jul 13, 07:29:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Angel: Thanks for sharing your personal story and comments. I try to make folks understand that the outcome with congenital CMV infection, even with primary infections as I am sure yours was, is highly variable. You are a special person. Thanks for reading!
At Sat Jul 21, 07:26:00 AM 2007,
channy_1985 said…
Angel: My son was born by emergency c-section 17 days ago because he had stopped moving and was found to have congenital cmv.
I am desperatly looking for people in the same position to talk to as i am terrified for my sons future.
Please email me at:
channy_1985@yahoo.com.au
Thanks, Chantelle.
At Mon Jul 23, 09:13:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Chantelle,
Below are links to the National Congenital CMV Disease Registry in the U.S. and another support group in the U.K. I hope this helps.
http://www.bcm.edu/pediatrics/index.cfm?Realm=99991126&This_Template=q_cmvsupportgroup
http://www.patient.co.uk/showdoc.asp?doc=26738769
Best of luck to you and your family.
Dr T
At Tue Oct 23, 07:00:00 PM 2007,
Tracy said…
I am 33 weeks along and found out at 29 weeks that my baby has congenital CMV. At my 18 week ultrasound we discovered that my baby had IUGR and echogenic bowel. I had blood work done at that time that showed IgG present so I was told that I had previously been infected but no IgM was shown at that time. My baby continued to fall into the smaller percentages being total less than 10th percentile with his head less than 3rd percentile. At 29 weeks I had an amnio done which confirmed high levels of CMV. I was told that this was a recurrent infection with very small chance of the baby having any symptoms. Since then the baby has an enlarged ventricle in his brain and fluid around his brain. The doctors are now saying they believe this is a primary infection because of all the symptoms that are present. My question is how can this be a primary infection if at 18 weeks IgG was present but no IgM? They are planning on inducing at 37 weeks and I am desparately trying to prepare myself for wait lays ahead.
At Fri Oct 26, 04:42:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Tracy Oct 23: This is almost CERTAINLY a primary CMV infection. The infection could have occurred early in the pregnancy or even just before conception and that's why the IgM was no longer present. The other possibility is that you became infected with another strain of CMV than what you might have had before. Any future pregnancies should be at very low risk for severe complications if you are otherwise healthy. Best wishes and we will be thinking about and praying for you. Dr T
At Wed Dec 12, 01:11:00 AM 2007,
johanna said…
Two weeks before conception CMV was found, IgG was 176 and IgM negative.
When I was 5 weeks pregnant I was tested again and my IgG level had raised to 190 and IgM was postive. According to my doctor it meant that I got a primary infection during the first weeks of pregnancy, but after reading your article I am not so sure . It seems quite complicated.
At Fri Dec 14, 03:54:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Johanna Dec 12: No,you had CMV BEFORE you ever conceived and that should put the current pregnancy at very low risk for the most severe complications related to congenital CMV infection. Remember, IgM is the first antibody type to respond to a new infection and that is followed by IgG. Since you had high IgG titers BEFORE conception, you must have contracted the virus before you got pregnant. That small increase in the IgM titer is not unusual with CMV and most providers do not know that. So, don't panic under these circumstances and if your doctor has any questions, have him/her give me a call. Good luck with your pregnancy and thanks for your question! Dr T
At Tue Jan 15, 09:54:00 PM 2008,
Edward said…
My son is in day care and was diagnosed with CMV when my wife was 24 weeks (SON - IGG 1.77, IGM 2.93) (POS >1.11, NEG <0.9). Therefore he was positive for IGG and IGM. One week after the detection my wife was tested for CMV ( WIFE – IGG 3.01, IGM 0.31) (POS >1.11, NEG <0.9) Therefore, she was positive for IGG and negative for IGM , as I understand it. We have previously seen a perineonatologist , and the ultrasounds looked fine. We are going to schedule another visit after news of the CMV. From what I read, CMV IGM stays in the body for 6-9 months. What determinations can we make regarding a primary or recurrent infection? What can be said for my son’s high level of IGM, and my wife’s low level of IGM? Is that a good indication that my wife did not contract it from my daycare son?
At Wed Jan 16, 07:35:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Edward Jan 15: Yes, your wife is immune to CMV and her immunity preceded your son's recent infection. Unfortunately, we don't know when she contracted CMV to begin with, eiether before or early in the current pregnancy. The odds are she got it before and if this baby is growing well, it is unlikely to be severly affected even if it does get a congenital CMV infection. I would suggest screening the baby for CMV within the week after delivery, and if the baby is CMV-positive, but otherwise 'normal' simply keep up with regular hearing and eye examinations. Thanks for your question. I am sure other readers will benefit from your experience. If you think of it, let me know how things turn out. Best wishes. Dr T
At Wed Feb 13, 07:14:00 PM 2008,
jrich78 said…
I am completely confused. I work in the hospital and was exposed to CMV but am unsure of when (Prior to or after conception). I'm currently 12 weeks pregnant. I called my MD for results but I do not know what to make of them. My Igg is 156 and my Igm is 1.5. I can't find numbers anywhere to help me figure this out. The ranges they gave me for Igg are 1-10 and Igm 0-.8. Mine are way outside. I think if I was exposed before my Igg would be high, but I don't know what a high number is. Does this seem like a primary or secondary exposure. Please help!
At Fri Feb 22, 06:29:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To jrich78: Unfortunately, with that high level of IgG, it is hard to say whether that is the result of a recent exposure (before or after you conceived) or simply the consequence of 'reexposure' and a secondary or 'anamnestic' antibody response (similar to what you would get with repeated doses of a vaccine). If the latter is true, then the baby is at low risk for a severe CMV infection. The IgM does not help us sort this out because it is such a low titere and as mentioned in my discussion, this could represent the tail-end of a primary infection or simply the periodic slight bump in IgM that can occur with CMV infetions, perhaps as a consequence of reactivation recurrences. You could find out (best done during the pregnancy by amniocentesis and PCR specific for CMV or after the pregnancy by sampling the baby's urine) if the baby has a congenital CMV infection, but as we also have discussed, unless the baby has some signs of severe disease (growth restriction and physical abnormalities, both detectable by ultrasound), we cannot predict the degree of compromise (IF ANY) might occur as a result of the infection. If the baby has this as the consequence of a simple reactivation recurrence on your part (while you had protective IgG), then usually the only follow-up needed is periodic vision and hearing checks and developmental milestones. Good luck. Let us know what you decide to do and the outcome. Thanks for writing and sorry I cannot be of more help at this time. Dr T
At Tue Mar 11, 12:42:00 PM 2008,
Anonymous said…
I have a question. My cousin’s daughter got CMV about a year ago from a Liver transplant. I saw her about 6 months latter at my wedding. 2 months after my wedding I got pregnant. My doctor never tested me for CMV, so I don't know if I had prior immunity or not. I was just concerned as to the risks to the baby sense I was exposed to CMV 2 months before my pregnancy. I amcurrently 18 weeks pregnant.
At Wed Mar 12, 06:00:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Mar 11: there is a reasonable chance you were/are already immune. And, if you had contracted the virus as a result of contact with that child, there is also a reasonable chance you developed protective immunity before you got far enough along in the pregnancy for it to be a major problem. If your pregnancy is going well and the baby is growing normally and has no abnormalities, channces are everything is fine. I do not even know if I would recommend testing you for CMV antibodies at this point, however, you may want to do that after the delivery because if you are NOT immune at that time, you are at increased risk for being exposed over time by your own child! If you spend anymore time with you cousin's daughter during the pregnancy you might also be a little more careful. CMV isn't contagious by air-borne transmission like the flu or chickenpox, but it is readily transmitted by body fluids. Good luck with your pregnancy and let us know how things turn out! Dr T
At Sat Mar 15, 01:24:00 PM 2008,
Anonymous said…
I have a 3 and 1/2 year old who is severely affected by cCMV. She got the full meal deal from this nasty virus. I am now 6 weeks pregnant. I have already had 2 boughts with fever and body aches and sore throat. Strep was diagnosed through testing the first time (2 weeks pregnant), and I don't have a diagnosis of why I experienced this second bout. I went to the doctor and had the flu and strep tests, and both were negative. Of course, I am freaking out about a possible reactivation or another strain of CMV. It is so early in my pregnancy. Please send me some helpful information. Should I have a CMV test? Thank you so much, Ashley
At Mon Mar 17, 07:27:00 AM 2008,
Anonymous said…
I lost my son to a primary cmv infection back in November 2007. I really want to try for another baby but my Consultant here in the UK says that I can not try until all evidence of IgM has gone from my bloods. Is that the case? If I wanted my Consultant to contact you as he has little or no information on cmv how best would he do that?
At Wed Mar 19, 07:00:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous March 17: You should have plenty of IgG (permanent immunity to CMV) at this point and should therefore be at VERY low risk for having a baby who is severely affected by CMV. IgM can hang around for a long time following CMV infections and can even reappear for reasons that are unclear. If you wait until you never have IgM, it may be a long time before you can try to get pregnant again. Your doctor can reach me through this website if he/she is concerned about my recommendation. Dr T
At Fri Mar 21, 06:45:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Ashley Mar 15: You don't need to have another CMV test done at this time. You had a baby with CMV, so you have CMV (and probably always will), but now you also have the immunity that should protect your current pregnancy from the more severe form of the infection that your first child had. Can this baby also get CMV? Yes and there is a 1-2% chance of that, but even if it does, he/she will probably do just need periodic follow-up of hearing and eye exams after birth. Best of luck and try to relax. The odds are in your favor that everything will be just fine! Dr T
At Tue Apr 22, 11:01:00 AM 2008,
Anonymous said…
I was recently told that i contracted CMV in my first or second month of pregancy. What are the chances that the baby will have CMV? If the fetus is infected with CMV, what are the chances of disabilities resulting from the virus?
At Tue Apr 22, 03:57:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Apr 22: Why do your doctors believe you contrcated CMV during your first or second month. Were you ill or did you simply have "exposure to CMV" and then had the antibody testing done? And, what were the actual test results. If you truly had a primary (very first time) infection with CMV during pregnancy, transmission rates range between 25-50% at some time during the pregnancy, but the actual affects on the baby are highly variable and somewhat unpredictable, ranging from death to no untoward effects whatsoever. To some degree, that is probably determined by the amount of protective immunity you had developed at the time the baby was actually exposed to the virus. You commented under one of my posts in September 2006 and I had one or two others that accompanied that one and several other follow-ups in repsonse t readers' questions since then. Check those out and then see if you have any other questions. The NIH also has a site devoted to CMV so you can look for that online as well. in fact, I think I have a link to that site in one of my posts. Good luck to you and let us know how things turn out. Dr T
At Wed Apr 30, 03:22:00 PM 2008,
Melissa said…
I am 35 weeks pregnant and was tested for the first time about 13 weeks ago for CMV. I have been tested 3 times now, and each result shows positive for IgM, but negative for IgG. Is it possible that the IgG would take so long to develop? Also, I was diagnosed a year ago with rheumatoid arthritis (no rheumatoid factor has ever been present). Could this illness have any affect on the CMV results?
Thank you.
At Thu May 01, 06:26:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Melissa Apr 30: Why were you first tested for CMV 13 weeks ago and what have those antibody titers done over time (increased, decerased, stayed the same?)? Also, why did your doctors think you had rheumatoid arthritis (i.e., what were the signs and symptoms at the time) and what kind of testing did you have done? Have you ever been screened for HIV, Epstein-Barr, or Parvovirus B19 virus infections?
It is not unusual to have a prolonged IgM response with primary CMV infections, but usually, by this time, most individuals will have at least some detecatble IgG as well. It is possible that you might have some 'defect' in your immune response that delays your reaction to CMV and perhaps other foreign antigens, especially if you have an underlying autoimmune disorder of some sort. It is also possible that you don't have CMV at all but have, instead, some other infection, or autoimmune condition, that produces antibodies that cross-react with CMV. This is all very fascinating to me, so any feedback you can give me would be MUCH APPRECIATED. I would recommend that you baby be tested shortly after birt to see if he/she has a congenital CMV infection. This is BEST DONE, not by serology, but by screening the baby's urine for the virus by culture or PCR techniques. The reason I am concerned is that if you really have CMV, and do not make IgG, then your baby will be born without any 'acquired protection' against the virus that it would have ordinarily gotten from you. IgG, but not IgM, crosses the placenta. Please stay in touch and let me know as you find things out. This is a very special area of interest to me. Thank you for writing and best wishes! Dr T
At Wed May 14, 08:06:00 AM 2008,
Melissa said…
Dear Dr. T -
Sorry about the delay in responding. I actually delivered the day after my post. My baby was early, but healthy. All of his functiioning is great and there are no signs of CMV (although I know that effects can happen much later). They did take urine and swab for PCR cultures for CMV, but the results are still pending.
As answers to some of your questions, the IgM levels stayed basically the same over the three tests. I was originally tested due to a slightly echogenic bowel for my baby in his sonogram (which the specialist then felt was flagged unnecessarily).
I was diagnosed with rhuematoid arthritis after experiencing continued joint swelling, pain, and stiffness. I was tested for HIV, Epstein-Barr, or Parvovirus B19 virus infections, with negative results. Since the symptoms were symmetrical and responded to the Plaquenil that I take, my rheumatologist continued with the RA diagnosis. I have since shared with him my CMV results, and he said he wasn't aware of any connection. I asked him to have me tested again in a little while, so that I can see if there are any IgG antibodies present.
I will get back to you when I find out the CMV results for my baby. If you have any suggestions of other testing or connection to autoimmune, I would appreciate it. Thanks for your time and interest!
--Melissa
At Thu May 15, 05:56:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Melissa: CMV infections can sometimes be associated with the transient production of autoantibodies. Let me know what the final test results are on your baby. Thanks again for writing and sharing your experiences. Dr T
At Sun Jun 01, 11:13:00 AM 2008,
Melissa said…
Dr. T -
My baby's results for CMV came back negative from both the urine and nasal swab. Just wanted to share that good news.
Thanks,
Melissa
At Tue Jun 03, 06:54:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Melissa: That IS good news. Thanks for letting me know. Have fun with your baby! Dr T
At Sat Jun 07, 02:23:00 PM 2008,
joanna said…
Hi there
I have just been diagnosed with CMV by my midwife and tested + for both IGG and IGM antibodies. At the time of the blood draw I was 6 weeks pregnant (6 weeks LMP). I have an appointment this Monday with a Perinatologist and will not find out the levels of each antibody until then. However, having done some reading on the topic (actually alot of reading because I am pretty worried!) I was wondering about the notion of testing for IGG Avidity in order to determine if I have a primary or recurrent infection. Here are my questions:
1) Could IGG adivity testing tell me anymore about my CMV infection (ie. primary VS recurrent)?
2) If so, what labs do the testing? I live in northern New Mexico and when I went on-line to look at the lab tests performed by the lab in my area it did not seem to do IGG avidity testing.
3) Is there any thing you can tell me about my the possibility of a congenital CVM infection in my baby given the info I have passed along? When I get the results of antibody testing on Monday I will forward the new info too.
4) Last one. I also have the disease Ulcerative Colitis and I had a really bad time with it this past winter. It was finally in remission by about the beginning of March and I got pregnant April 9-10 (I was charting so know when I ovulated). I read about some associations between colitis and CMV and you have discussed autoimmune diseases (big debate as to whether UC is autoimmune) in relation to worsened or recurrent CMV and a greater liklihood of a more severe congential infection if it occurs. Do you have any info on CMV and UC? Does the fact that I have UC shed any more light on my pregnancy and CMV?
Thank you for your time. Actually, your writing on this topic is the most comprehensive and helpful that I have found so far.
Joanna
At Tue Jun 17, 04:20:00 PM 2008,
River said…
Dear Doc, I was diagnosed with CMV in February whilst pregnant. I miscarriaged at about 7weeks and have been advised not to get pregnant again for at least 4-6 months from infection. However, they have no idea when I may have been infected; I have had symptoms since last august which have continued on and off to date including lumps in neck and/or armpits and headaches, fatigue and lost of appetite. The last blood test results showed both IgG and IgM to be present and a low virus load of < 10 copies.
The question is: why am I still having symptoms and when will it actually be safe to conceive again in light of my persistent symptoms. Awaiting latest blood result due next week. What should I be looking for? Thanks River
At Sat Jun 21, 05:55:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To River: I am NOT worried about the CMV at this point, but I AM worried about your other complaints. Have you been screened for HIV and Epstein-Barr virus? Have you had any blood work done to look at your white blood count and morphology, liver function tests, thyroid function, blood sugar, etc. Have you seen a hematologist to check out those lymph nodes. They may need to be biopsied. My point is this, get in to see someone who will look past the CMV infection that probably had NOTHING to do with your miscarriage! Please let us know what you find out. Dr T
At Mon Jun 23, 10:14:00 PM 2008,
Anonymous said…
Dear Doctor Trofatter,
I am going in my 20th week of pregnancy and I had the Igg and Igm antibody screens done last week as a preventative measure because we are going to have a child at my jobsite with active CMV in the coming weeks. I was told I am "immune" based on my Igm results being negative (no value given) and my Igg being positive (1.91 was the value). My OB could only tell me that I have not recently gotten the CMV virus but that I could have gotten it within the past 4-6 months. Can you tell me how she came to this conclusion? I am a little worried because I have been pregnant for 5 months which means there is a possibility I contracted it during early pregnancy. Is there really any way of knowing when I contracted CMV based on the Igg level? For instance, does it go up with time? Thank you very much for your time. I look forward to your response.
At Thu Jun 26, 06:01:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous June 23: Yes, you could have gotten it in the last 6 months, but more likely you had it BEFORE you ever got pregnant - most people do, especially if they work around young children. The IgG titers usually do not fluctuate much with time. If I were you, I would be comforted rather than scared by the results! Good luck for the rest of the pregnancy! Dr T
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